The human brain and nervous system begin forming very early in prenatal life and continue to develop through adolescence. Environmental factors during this time in development can have lifelong effects on overall brain and nervous system health. Accordingly, some nutrients have become known to be increasingly important in the diets of infants, children and pregnant and lactating women because of their ability to promote early brain development and help prevent or reduce brain and nervous system injury or illness.
Magnesium, as a bivalent cation, i.e. Mg2+, is the fourth most abundant ion in the body and serves as a co-factor for more than 300 enzymes. Magnesium is a cofactor for energy metabolism, nucleic acid synthesis and is implicated in regulation of neuronal activity. Magnesium is essential for proper functioning of the cardiovascular, neuromuscular and nervous systems.
Evidence suggests that about one third of dietary magnesium is absorbed from the gastrointestinal tract. The bulk of magnesium absorption takes place in the upper small bowel. Absorption is by means of an active process apparently related to the transport system for calcium. Ingestion of low amounts of magnesium results in increased absorption of calcium and vice versa. Therefore, one potential benefit of providing a more bioavailable form of magnesium would be that less magnesium is needed in a nutritional formulation(s), which may indirectly enhance calcium absorption which is known to be important for both brain and skeletal system development. Accordingly, providing a nutritional composition including a more bioavailable magnesium and calcium may have synergistically affect neural health and development.
Magnesium is a cofactor of all enzymes involved in phosphate transfer reactions that utilize adenosine triphosphate (“ATP”) and other nucleotide triphosphates as substrates. Hypomagnesia causes increased central nervous system (“CNS”) irritability, disorientation, and convulsions. Further, abnormally low concentrations of magnesium in the extracellular fluid result in increased acetylcholine release and increased muscle excitability that can produce tetany. Magnesium deficiency is also associated with oxidative neuronal cell death. Therefore, ensuring a maximal and prolonged supply of magnesium, via the use of MgT, to a developing infant or child could theoretically serve as a preventative measure to protect and conserve maximal nervous system health.
Within the brain, magnesium functions as a regulator of N-methyl-D-aspartate (“NMDA”) receptors, which are critical for synaptic plasticity, and thus memory formation and consolidation (Slutsky, I., et al., Enhancement of Learning and Memory by Elevating Brain Magnesium. Neuron 65, 165-177: 2010). More specifically, magnesium has been shown to antagonize NMDA receptors, thus high levels of magnesium may reduce post-trauma neuronal damage and result in improved neurological outcome.
Magnesium sulfate therapy has been suggested as a neuroprotective therapy against the negative effects of preterm birth (Mercer, B., et al., Magensium Sulfate for Preterm Labor and Preterm Birth. Obstetrics & Gynecology, 114:3, 650-668: 2009). However, such approaches may be limited by the relative lack of bioavailability of magnesium sulfate and other magnesium salts. Therefore MgT may be of particular importance in the preterm infant, which is known to be at high risk for neurological insults and nutritional deficiencies.
It has been shown that a 3-fold increase of magnesium sulfate intravenous infusion for 5 days in rats failed to increase brain concentrations of magnesium (Kim et al., The effects of plasma and brain magnesium concentrations on lidocaine-induced seizures in the rat. Anesthesia & Analgesia. 1996 83:1223-1228). In adult humans, a 100%-300% increase in blood magnesium corresponded only to a 10-19% elevation in corresponding cerebrospinal fluid levels of magnesium (McKee, J. A., et al., Analysis of the brain bioavailability of peripherally administered magnesium sulfate: A study in human with acute brain injury undergoing prolonged induced hypermagnesemia. Critical Care Medicine. 2005 33:661-666). Therefore it has been historically difficult to modulate brain magnesium through supplementation.
It is now proposed that MgT may have an even more significant impact on nervous system health when delivered early in life when all of the fundamental aspects of the nervous system are being built to support functions required later in life. Therefore pediatric subjects who consume nutritional products that comprise magnesium sources other than MgT may not be obtaining optimum nutrition essential for brain and nervous system development.
Accordingly, it would be beneficial to provide a nutritional composition that contains MgT. More specifically, it would be beneficial to provide pediatric nutritional compositions comprising MgT since brain and nervous system growth and development are critical during the first years of life. Additionally, it is beneficial to provide a method of promoting neurological health and GI tolerance in a pediatric subject by providing a nutritional composition comprising MgT.